Aminoethyl oximes

ABSTRACT

The compound of the formula ##STR1## wherein R 6  is H or Halo and R is alkoxy or alkyl thio, having, with (CH 2 )n a total of up to eight carbon atoms are described as having antidepressant as well as sedative activity.

This application is a continuation of U.S. application Ser. No. 600,808,filed Apr. 16, 1984, now abandoned, which is in turn a continuation ofSer. No. 171,695 filed Jul. 24, 1980, which is a division of applicationSer. No. 875,433 filed Feb. 6, 1978, now U.S. Pat. No. 4,235,931 whichis a division of application Ser. No. 639,571 filed Dec. 10, 1975, nowU.S. Pat. No. 4,192,818 which is a division of application Ser. No.517,519 filed Oct. 24, 1974, now U.S. Pat. No. 3,937,841 which is adivision of application Ser. No. 279,971 filed Aug. 11, 1972, nowabandoned, which is a division of application Ser. No. 715,571 filedMar. 25, 1968, now U.S. Pat. No. 3,692,835.

The invention relates to new compounds of formula I ##STR2## and saltsthereof with pharmaceutically acceptable acids, in which formula all thesubstituents may be hydrogen, while R₁ and R₂ may furthermore be amethyl group, R₃ an alkyl group, an alkoxy-alkylene group, analkylthioalkylene group, an alkylsulphoxyalkylene group or analkylsulphonalkylene group having up to 8 carbon atoms or a benzylgroup, and R₄, R₅ and R₆ a halogen atom, an alkyl group, an alkoxy groupor an alkylthio group having up to 6 carbon atoms, a benzyloxy group,--OH, --NH₂, a mono- or dialkylamino group, in which the alkyl group(s)contain(s) 1 or 2 carbon atoms, --CN or --CF₃, and two of thesubstituents R₄, R₅ and R₆ may each represent a metanitro group ortogether a trimethylene group, a tetramethylene group, a methylene dioxygroup, an ethylene dioxy group, a benzo group, a pyridino group, anindeno-1,2-, a 1,4-benzthiazino-2,3 group or a 1,4-benzoxthiino-2,3group, with the exception of the HCl salt of the compound in which R₅and R₆ each represent an orthochlorine atom and R₁, R₂, R₃ and R₄ eachrepresent hydrogen.

The compounds according to the invention have interestingpharmacological properties. They have in particular a very strongcentral activity which may be expressed both in an anti-depressiveactivity, whether or not caused by monoamino oxidase inhibition, and ina sedative or anticonvulsive activity.

In particular those compounds according to the invention in which bothR₁ and R₂ represent a hydrogen atom have a strong activity.

The monoamino oxidase inhibiting effect of compounds of formula I wasfound in experiments in which a quantity of the compound to be testedwas administered intraperitoneally or orally to five male albino mice.One hour after the administration the animals were injectedsubcutaneously with tryptamine hydrochloride in a quantity of 250mgms/kgm. This quantity caused no mortality in animals which had notreceived the compound to be tested but dis cause mortality in theanimals which had been treated. Eighteen hours after the administrationof tryptamine hydrochloride it was determined how many treated animalshad died. The ED₅₀ was determined from the results.

The antidepressive effect of compounds of formula I was also determinedin the tetrabenazine test. In this test a quantity of the compound to betested was administered intraperitoneally or orally to five male albinomice. After 45 minutes the animals were injected subcutaneously with 80mgms per kgm of tetrabenazine. After another 45 minutes the degree ofptosis was determined and compared with the ptosis of animals which hadreceived tetrabenazine alone. The ED₅₀ was determined from the results.

The sedative effect of compounds according to the invention was found inthe hexobarbital narcotising test. In this test a compound to be testedwas administered intraperitoneally and orally, respectively, 60 minutesprior to a dose of hexobarbital (30 mgms/kgm) which was just less thannarcotic. Induction of narcosis was the criterion for the activity ofthe substance. The ED₅₀ was calculated from a series of experiments withvarying dosages.

The anticonvulsive effect of compounds according to the inventionagainst supramaximal electric shock was determined in female mice 30minutes after an intraperitoneal administration or 60 minutes after anoral administration of the compound to be tested.

The influence of compounds on the convulsive effect of a supramaximalintravenously administered dose of pentamethylene tetrazol (50 mgms/kgm)was also determined in female mice 30 minutes after an intraperitonealadministration or 60 minutes after an oral administration of a compound.

The antidepressive compounds according to the invention are particularlysuitable for use in the therapy of neurotic and psychotic disturbances,in particular of the depressive syndrome and also for the treatment ofpsychosomatic disturbances. The substances may therefore be administeredto depressive patients as a psychostimulant.

The sedative compounds are excellently suitable for use as an ataractic.They may successfully be used for the treatment of mild psychoneuroticphenomena.

The anti-convulsive compounds may be used in the treatment of epilepticpatients.

The compounds, including the HCl salt of O-(2-amino-ethyl)2,6-dichlorobenzaldoxim, may be administered in the conventional mannersafter having been brought in a suitable form of administration. They maybe injected or be administered orally or rectally. As forms ofadministration are therefore to be considered inter alia: injectionliquids, pills, tablets, coated tablets, capsules, powders, and thelike.

The way in which, the quantity in which and the frequency with which thesubstances are to be administered to the patient may vary for eachindividual patient also in accordance with the severity of thedisturbances. In general, the practitioner will have no trouble inchoosing the correct therapy for a given patient.

The dosing of sedative and antidepressive compounds will in general befrom 10 to 500 mgms daily for adults. As a rule a quantity of from 10 to150 mgms will be sufficient.

Anti-convulsives according to the invention will generally beadministered in dosages of from 100 to 500 mgms daily.

The compounds according to the invention, including the HCl salt ofO-(2-aminoethyl)2,6-dichlorobenzaldoxim may be processed according tomethods commonly used in pharmacy to compositions, for example, bymixing an active substance with or dissolving it in solid or liquidcarriers.

As such are to be considered the conventional carriers, for example,water made isotonic with blood, if desired, for example, by means ofkitchen salt, glycerin, chalk, calcium phosphate, lactose, powderedsugar, calcium carbonate. As swelling agents in tablets and coatedtablets may be used, for example, potato starch, maize starch, arrowroot (amylum marantae), carboxy methylcellulose, gelatin and acacia gum.

As lubricants may be used talcum, magnesium stearate, calcium stearate,and stearic acid. Compositions for oral administration may contain inaddition flavouring substances, for example, sugars or vanilla extract.

As preservatives may be used, for example, propyl-p-hydroxybenzoate andbenzyl alcohol. The compositions may contain in addition surface-activesubstances, for example, mono-, di- and tri-esters of higher fattyacids.

As examples of pharmaceutically acceptable acids with which thecompounds can form salts may be mentioned: hydrohalogenic acids, forexample, hydrochloric acid, hydrobromic acid, in addition otherinorganic acids, for example, sulphuric acid, nitric acid, phosphoricacid, and organic acids, for example, citric acid, acetic acid, oxalicacid, fumaric acid, lactic acid, succinic acid, sulphamic acid, benzoicacid, tartaric acid, gallic acid.

The compounds according to the invention may be prepared according tomethods which are known per se.

The invention therefore also relates to a method of preparing new oximethers, characterized in that compounds of formula: ##STR3## and saltsthereof with pharmaceutically acceptable acids, in which formula all thesubstituents may be hydrogen while R₁ and R₂ may furthermore represent amethyl group, R₃ an alkyl group, an alkoxyalkylene group, analkylthioalkylene group, an alkylsulphoxyalkylene group, analkylsulphonalkylene group having up to 8 carbon atoms or a benzylgroup, and R₄, R₅ and R₆ may each be a halogen atom, an alkyl group, analkoxy group or an alkylthio group having up to 6 carbon atoms, abenzyloxy group, a hydroxy group, an amino group, an alkylamino group ora dialkylamino group, in which the alkyl group(s) contain(s) 1 or 2carbon atoms, a nitrile group or a trifluoromethyl group and two of thesubstituents R₄, R₅ and R₆ may each be a meta nitro group or together atrimethylene group, a tetramethylene group, a methylenedioxy group, anethylenedioxy group, a benzo group, a pyridino group, an indeno-1,2group, a 1,4-benzthiazino-2,3 group or a 1,4-benzoxthiino-2,3 group,with the exception of the HCl salt of the compound in which R₅ and R₆each represent an orthochlorine atom and R₁, R₂, R₃ and R₄ eachrepresent a hydrogen atom, are prepared according to methods which areknown for the preparation of this type of compounds and according tomethods analogous thereto.

For example, compounds according to the invention may be prepared byreacting a compound of formula II ##STR4## wherein M is a hydrogen atomor an alkali metal atom, with a compound of formula III ##STR5## whereinX is a halogen atom, preferably a bromine or chlorine atom or a tosyloxygroup and Y is a hydrogen atom or an acyl group, for example, analkoxycarbonyl group or a carbobenzoxy group, which, after the couplingreaction, is split off by hydrolysis.

The reaction may be carried out in a suitable solvent. As such are to beconsidered inter alia: alcohols, for example, methanol, ethanol,ketones, for example, acetone and methylethyl ketone, and ethers, forexample, dioxane, dimethylglycol ether.

When M in formula II is a hydrogen atom, it may be recommendable to addan acid binder to the reaction mixture. As such may be mentioned interalia alcoholates, potassium carbonate and sodium carbonate, tertiaryamines, pyridine and the like.

The temperature of the reaction mixture may vary between rather widelimits. As a rule, however, it will be between 0° and 50° C.

The oxims of formula II may be obtained in the conventional manner fromthe corresponding aldehydes or ketones by means of hydroxylamine. Theoximates may be prepared from the oxims by adding the oxims, whether ornot dissolved in alcohol, to a solution of potassium or sodiumalcoholate or -hydroxide in alcohol.

The compounds according to the invention may alternatively be obtainedby reacting a compound of formula IV ##STR6## with a compound of formulaV ##STR7## wherein Y is a hydrogen atom, or an acylgroup for example analkoxycarbonyl group or a carbobenzoxy group which, after the couplingreaction, is split off by hydrolysis.

The reaction may be carried out in a suitable solvent. As such may bementioned: alcohols, pyridine, dioxane, dimethylformamide,tetrahydrofurane and the like or mixtures thereof. In general thereaction temperature lies between room temperature and the boiling pointof the solvent. An alternative method of preparing compounds accordingto the invention is that in which an oxim of formula II (M=H) is reactedwith an imine of formula VI ##STR8## wherein R'₁ is an acyl group whichis split off after the reaction by hydrolysis.

The reaction may be carried out in a suitable solvent, for example,dioxane, benzene.

The compounds according to the invention may also be obtained byreacting a compound of formula VII ##STR9## wherein X is a halogen atom,preferably a bromine atom or a tosyloxy group, with ammonia ormethylamine.

The reaction may be carried out, for example, in alcohols.

The starting substances of formula VII may be obtained by reacting oximsof formula II (M=H) in the presence of an acid binder with a halogencompound of formula VIII ##STR10## wherein X has the same meaning as informula VII and Hal is a halogen atom, preferably a bromine atom. Whenin formula II one or more of the substituents R₄, R₅ and R₆ is a primaryor secondary amino group and a hydroxy group, respectively, it ispreferably protected with an acyl group and a benzyl group,respectively, which groups are subsequently split off by hydrolysis orhydrogenolysis.

In order that the invention may be readily carried into effect certainexamples thereof will now be described in greater detail.

1. 4'-methyl-O-(2-aminoethyl)acetopheneno oxim-HCl

A solution of 3.23 gms of O-(2-aminoethyl) hydroxylamine dihydrochlorideand 3.35 gms of 4'-methylacetophenone in a mixture of 15 mls of pyridineand 30 mls of absolute ethanol was refluxed for 2 hours. The solvent wasthen distilled off in vacuo and the residue, after dissolving in littlewater, was washed three times with diethyl ether. 30 mls of 2N sodiumhydroxide solution were then added to the washed solution and the wholewas again extracted three times with ether. This ether extract waswashed three times with water and then dried on sodium sulphate. Afterdistilling off the solvent in vacuo the residue was neutralised withalcoholic hydrochloric acid. From this neutralised solution thehydrochloride of 4'-methyl-O-(2-aminoethyl)acetophenone oximcrystallised after the addition of ether. The product was crystallisedagain from a mixture of absolute ethanol and ether, melting point183°-185° C.

2. O-(2-aminoethyl)-3',4'-ethylene-dioxy-acetophenone oxim-HCl

4.8 gms of 3',4'-ethylenedioxyacetophenone oxim were added to a solutionof 0.100 mol of sodium (2.30 gms) in 75 mls of absolute ethanol. Theoxim dissolved. 0.050 mol of 2-bromoethylaminohydrobromide were thenadded (10.25 gms). The mixture was stirred at room temperature for 2hours. Then it was sucked off from the NaBr formed and the filtrate wasevaporated in vacuo until it was free from solvent. The residue wasdissolved in water (50 mls) and ether (50 mls) and the water layer wasseparated. The ethereal layer was washed two times with 25 mls of waterand dried on Na₂ SO₄. The ether was removed in vacuo, an oil beingformed. This oil was dissolved in approximately 20 mls of absolutealcohol and acidified with alcoholic hydrochloric acid. By the additionof ether the HCl salt crystallised out. After cooling the crystallisedsubstance was sucked off. After crystallisation from alcohol the meltingpoint was 203°-206° C.

3a. O-(2-bromoethyl)4'-methylhexanophenone oxim

20.5 gms of 4'-methylhexanophenone oxim were dissolved in a solution of4.6 gms of sodium in 100 mls of absolute ethanol. At 20° C. and whilestirring this solution was added to a mixture of 60 mls of 12,dibromoethane and 50 mls of N,N-dimethylformamide. The reaction mixturewas then heated to 65° and kept at this temperature for 16 hours. Theformed precipitate was then sucked off and the filtrate was concentratedin vacuo. After the addition of 200 mls of water the concentrate wasextracted with chloroform (2×100 mls). The extract was dried on sodiumsulphate, concentrated in vacuo and then distilled in a high vacuum(0.005 mm). The distillate (boiling point 111°-114° C./0.005 mm)contained, in addition to 4'-methyl-hexanophenone oxim, theO-(2-bromoethyl)-4'-methylhexanophenone oxim.

b. O-(2-aminoethyl)4'-methylhexanophenone oxim. HCl

A solution of 9.0 gms of this distilled bromine compound in 50 mls ofethanol was mixed with 50 mls of concentrated ammonia. This mixture wasthen stirred in a closed vessel at 65° for 16 hours and thenconcentrated in vacuo. The concentrate was mixed with 50 mls of etherand then extracted three times with 20 mls of N hydrochloric acid. Theacid extract was washed with 50 mls of ether, then rendered alkalinewith 40 mls of 2N sodium hydroxide solution and again extracted threetimes with 30 mls of ether. This ethereal extract was dried on sodiumsulphate, concentrated, and the remaining oil was distilled in a highvacuum. The distillate (boiling point 121°-122° C./0.3 mm) was taken upin 25 mls of diethylether and neutralised with 2N ethanolic hydrochloricacid as a result of which the above substance crystallised out. Aftercrystallisation from ethyl acetate the melting point was 97°-98° C.

4a. O-(2-p.toluene sulphoxyloxy ethyl)-4'-methyl propiophenone oxim

12.7 gms of p-toluenesulphonylchloride were added to a solution of 13.8gms of O-(2-hydroxyethyl)-4'-methyl propiophenone oxim (synthetised from4'-methylpropiophenone oxim and ethelene oxide under the influence oflithium ethanolate in ethanol) in 20 mls of pyridine while stirring andcooling in ice water. The reaction mixture was stirred while cooling foranother 15 minutes and then at room temperature for 3 hours. Thereaction mixture was then poured on a mixture of 90 gms of ice and 30mls of concentrated hydrochloric acid. The separated solid was extractedthree times with 50 mls of benzene. The solution in benzene was washedwith 2N hydrochloric acid and then with dilute sodium carbonatesolution. After drying the solution on potassium carbonate the solventwas removed in vacuo and the residue crystallised from a mixture of 35mls of benzene and 55 mls of petroleum ether.

b. O-(2-aminoethyl)-4'-methyl propiophenone oxim HCl

A suspension of 3.6 gms of the compound prepared sub 4a in 100 mls ofconcentrated ammonia and 100 mls of ethanol was shaken at roomtemperature for 15 hours and then at 80° for another 7 hours in anautoclave. The excessive ammonia and a part of the solvent weredistilled off in vacuo until the residue turned cloudy. After theaddition of 15 mls of 2N sodium hydroxide solution, this residue wasextracted 3 times with totally 100 mls of ether. The ether extract wasthen extracted 2 times with 10 mls of 2N hydrochloric acid. This acidextract was again made alkaline with 5 mls of 50% sodium hydroxidesolution and then extracted with totally 30 mls of chloroform. Thisextract was dried on sodium sulphate after which the solvent was removedin vacuo. The residue was distilled in a high vacuum. By neutralisingthe distillate with 6 mls of alcoholic hydrochloric acid and then adding30 mls of ether, a crystalline substance was obtained. Melting pointafter recrystallisation from diethylether 124.5°-125.5° C.

5a. O-{2-(N-ethoxycarbonylamino)ethyl}-4'-methylthioacetophenone oxim

A solution of N-ethoxycarbonylethylene imine, obtained by reacting 1.4mls of ethylene imine with 2.4 mls of ethylchloroformate under theinfluence of triethylamine in 30 mls of absolute benzene was mixed,while stirring, with a solution of 4.1 gms of 4'-methylthioacetophenoneoxim in benzene. The reaction mixture was then heated to the boilingtemperature while stirring and then it was stirred at this temperaturefor another 30 minutes. After leaving the mixture to stand at roomtemperature for 16 hours it was mixed with water and the benzene layerwas then separated. This benzene layer was washed 3× with water and thendried on sodium sulphate. After removing the solvent the above-mentionedsubstance was obtained by fractional crystallisation from ethanol andpetroleum ether.

b. O-(2-aminoethyl)-4'-methylthioacetophenone oxim HCl

Of this ethoxy carbonyl compound 0.21 gms were dissolved in 4 mls ofethanol. After the addition of 2.0 mls of 3N sodium hydroxide solutionthis solution was refluxed for 4 hours. The solvent was then partlyremoved in vacuo and the residue extracted 3× with ether after theaddition of some water. The ethereal solution was shaken with 2.00 mlsof 1.2N hydrochloric acid and, after the layers had separated, onceagain with water. 1.8 ml of 3N sodium hydroxide solution were added tothe acid extract and the latter was extracted again two times withether. This latter ether extract was dried on sodium sulphate, thenevaporated, and the resulting residue neutralised with alcoholichydrochloric acid after which the substance crystallised. Aftercrystallisation from ethanol/diethyl ether 1:1 the melting point was215°-219° C.

6. O-(2-amino-ethyl)-acetophenone-oxim hydrochloride

0.050 mol of acetophenone oxim (6.75 gms) were added to a solution of0.200 mol of sodium (4.60 gms) in 75 mls of ethanol supra 0.100 mol of2-bromoethylamine hydrobromide (20.5 gms) were then added after whichthe mixture was stirred at room temperature for 2 hours. The formed NaBrwas then sucked off and the filtrate was evaporated in vacuo until freefrom solvent. The residue was dissolved in 75 mls of ether+75 mls ofwater, the water layer was separated and the ether layer was washed twotimes with 25 mol of water. Subsequently the ether layer was extractedwith 50 mls of 2N HCl and then with 20 mls of water. The acid extractswere made basic with 75 mls of 2N NaOH and then extracted three timeswith 50 mls of ether. The collected ether extracts were washed threetimes with 20 mls of water and dried on Na₂ SO₄. The ether wasevaporated in vacuo as a result of which an oil was obtained. This oilwas dissolved in 5 mls of absolute alcohol and acidified to pH 4 withalcoholic hydrochloric acid. A crystalline substance precipitated as aresult of the addition of ether. This substance was sucked off anddried, and recrystallised from a mixture of absolute alcohol and ether.Melting point 173°-175° C.

7. O-(2-amino-ethyl)-methyl-α-naphthyl-ketoxim-hydrochloride

0.025 mol of methyl-α-naphthyl-ketoxim (4.63 gms) were added to asolution of 0.100 mol of sodium (2.30 gms) in 75 mls of absoluteethanol. The oxim dissolved. 0.050 mol of 2-bromoethylamine hydrobromide(10.25 gms) were then added. The mixture was stirred at room temperaturefor 2 hours. The formed NaBr was sucked off and the filtrate wasevaporated in vacuo until free from solvent. The residue was dissolvedin water (50 mls) and ether (50 mls) and the water layer was separated.The ether layer was washed two times with 25 mls of water and dried onNa₂ SO₄. The ether was removed in vacuo in which an oil was formed. Thisoil was dissolved in approximately 20 mls of absolute alcohol andacidified with alcoholic hydrochloric acid. By the addition of ether theHCl salt crystallised. After cooling this was sucked off. After tworecrystallisations from alcohol the melting point was 236°-238° C.

8. O-(2-amino-ethyl)-isobutyrophenone oxim hydrochloride.

0.050 mol of isobutyrophenone oxim (8.15 gms) were added to a solutionof 0.200 mol of sodium (4.60 gms). This oxim dissolved substantiallyentirely. This was mixed with 0.100 mol of 2-bromoethylaminehydrobromide (20.5 gms). The mixture was stirred at room temperature for2 hours. Then it was sucked off from the formed precipitate of NaBr andthe filtrate was evaporated in vacuo until it was free from solvent. Theresidue was dissolved in 75 mls of ether, the water layer was extractedand the ether layer was washed 2 times with 25 mls of water. The etherlayer was then acidified with 50 mls of 2N HCl, then separated andextracted once again with 25 mls of water. The acid extracts were madebasic with 75 mls of 2N NaOH and extracted three times with 50 mls ofether. The collected ether extracts were washed three times with 25 mlsof water and dried on Na₂ SO₄. After removing the ether in vacuo acolourless oil remained. This was dissolved in 10 mls of absolutealcohol. The solution was acidified with alcoholic hydrochloric acid topH 4 after which ether was added and a crystalline substanceprecipitated. This was sucked off and dried, after cooling. Meltingpoint 90.5°-92.5° C.

The following compounds were obtained in an analogous manner accordingto:

method A: compound of formula II+compound of formula III

method B: compound of formula IV+compound of formula V.

    __________________________________________________________________________     ##STR11##                                                       anti- anti-    R.sub.3  R.sub.4      R.sub.5                               R.sub.6                                    Meltpoint °C.                                             method                                                  sedative                                                       convulsive                                                             depressive    __________________________________________________________________________             2.OCH.sub.3            110,5-111                                             A    -    +     +             2.OC.sub.4 H.sub.9     70       B    +    +     -             3,4-OCH.sub.2 O        187-188  A    -    -     +    CH.sub.3 4.CH.sub.3             183-185  vbl             +    CH.sub.3 2.CH.sub.3   4 CH.sub.3                                    137-140  A    -    -     +    CH.sub.3 3,4-CH.sub.2CH.sub.2CH.sub.2                                    193-195  B    -    +     +    CH.sub.3 3,4-OCH.sub.2CH.sub.2O 203-206  vb2  -    +     +    CH.sub.3 4SCH.sub.3             215-219  vb5       +     +    CH.sub.3 3Cl          4 OCH.sub.3                               5Cl  158-159  A    -    +     +    CH.sub.3 3,4-pyridino-2,3       235-237  B    -          +    CH.sub.3 3,4-indeno-2,3         257-265  B               +    CH.sub.3 2,3-benzo         4OCH.sub.3                                    174-175  A         +     +    CH.sub.3 3,4-benzoxthi-         190-195  B               +             ino-2,3    C.sub.2 H.sub.5             3CH.sub.3              157-159  B               +    C.sub.2 H.sub.5             4CH.sub.3              124,5-125,5                                             vb4  -    -     +    nC.sub.3 H.sub.7             4CH.sub.3              82-83    B               +    nC.sub.3 H.sub.7             2,3 benzo         4OCH.sub.3                                    148-149,5                                             A    -    +     +    nC.sub.5 H.sub.11             3CH.sub.3              kpt.base 116-B           +                                    118/0,03    nC.sub.5 H.sub.11             4CH.sub.3              97-98    vb3  -    +     +    nC.sub.5 H.sub.11             3CH.sub.3    4CH.sub.3 86,5- 88 B               +    nC.sub.5 H.sub.11             3,4-OCH.sub.2O         105      A    -    -     +    nC.sub.5 H.sub.11             4-SCH.sub.3            131,5-133                                             A    +    -     +    nC.sub.5 H.sub.11             2OH                    94-96    B               +    nC.sub.5 H.sub.11             4OH                    80-84    B               +                                    maleaat    nC.sub.5 H.sub.11             4CF.sub.3              96-100   A    +    -     +    nC.sub.5 H.sub.11             2Cl          4CH.sub.3 oil, base                                             B               +    nC.sub.5 H.sub.11             3Cl          4CH.sub.3 50       B               +    nC.sub.5 H.sub.11             3Cl          4OH       142-143 base                                             B               +    nC.sub.5 H.sub.11             2CH.sub.3    4Cl  5CH.sub.3                                    122-123  B               +    nC.sub.5 H.sub.11             2NH.sub.2              oil base B               +    nC.sub.5 H.sub.11             4NH.sub.2              oil base B    -          +    nC.sub.5 H.sub.11             3NH.sub.2    4CH.sub.3 kpt 136-8/0,05                                             B               +                                    base    nC.sub.5 H.sub.11             4CN                    kpt 124-8/0,01                                             B               +                                    base    CH.sub.2 C.sub.6 H.sub.5        176-176,5                                             A    -    +     +    CH.sub.2SC.sub.3 H.sub.7        100-101  A    -    -     +    CH.sub.2SOC.sub.3 H.sub.7       144-146  B               +    CH.sub.3                        173-175  vb6  -    +     +    CH.sub.3 2,3-benzo              236-238  vb7             +    i.C.sub.3 H.sub.7               90,5-92,5                                             vb8  -    -     +    H        H            H    H    142-124  A    -    +     +             2CH.sub.3              142,5-144,5                                             A    -    +     +             2nC.sub.4 H.sub.9      93,5-95  B    +    +     -             3OCH.sub.3             129-130  A    -    +     +             4OCH.sub.3             159-160  A    -    +     +             4OCH.sub.2 C.sub.6 H.sub.5                                    213-214  A               +             2Cl                    128-129,5                                             A    +    -     +             4Cl                    193-195  A    -    +     +             2Cl          4Cl       179-181  A    -    +     +             2Cl          6Cl       120      A    -    +     +             2Br                    135,5-136,5                                             A    -    +     +             4N(CH.sub.3).sub.2     186,5-187                                             A    +    +     +    CH.sub.3 4OCH.sub.3             189-191  A    -    -     +    CH.sub.3 3OCH.sub.3   4OCH.sub.3                                    212-214  A    +    -     +    CH.sub.3 2CH.sub.3    4OCH.sub.3                                    157-158  A    -    +     +    CH.sub.3 4Cl                    192-194  B               +    CH.sub.3 3,4-benzo              237-240  A    +          +    C.sub.2 H.sub.5                 152-154  A    -    -     +    C.sub.2 H.sub.5             2CH.sub.3              62-64    B               +    C.sub.2 H.sub.5             4OCH.sub.3             152-153  A    +    -     +    C.sub.2 H.sub.5             4OC.sub.2 H.sub.5      145-146  A    -    -     +    C.sub.2 H.sub.5             4OnC.sub.4 H.sub.9     158,5-159,5                                             A    -    +     +    C.sub.2 H.sub.5             4Cl                    150-151  A    -    -     +    C.sub.2 H.sub.5             2Cl          4OCH.sub.3                                    130-131  A    -    +     +    C.sub.2 H.sub.5             3F           4OCH.sub.3                                    180      A    -    -     +    C.sub.2 H.sub.5             3NO.sub.2              188-189  A    -    -     +    C.sub.2 H.sub.5             2NO.sub.2    4OCH.sub.3                                    197-198  A    -    -     +    nC.sub.3 H.sub.7                94,5-95,5                                             A    -    -     +    nC.sub.3 H.sub.7             4Cl                    82-84    B               +    C.sub.3 H.sub.5             4F                     95,5-97,5                                             A    -    -     +                                    maleaat    nC.sub.4 H.sub.9                82,5-84  A    -    +     +    nC.sub.4 H.sub.9             2Cl                    127- 132/0,15                                             B               +                                    kpt base    nC.sub.4 H.sub.9             4Cl                    96-98    B    nC.sub.4 H.sub.9             2,3-benzo              oil, base                                             B               +    nC.sub.5 H.sub.11               93,5-94  A    -    +     +    nC.sub.5 H.sub.11             2CH.sub.3              150/0,07 B    -          +                                    kpt base    nC.sub.5 H.sub.11             3OCH.sub.3             79-80    B               +    nC.sub.5 H.sub.11             2Cl                    oil, base                                             A    -    -     +    nC.sub.5 H.sub.11             3Cl                    98,5-99,5                                             A    -    -     +                                    maleaat    nC.sub.5 H.sub.11             4Cl                    88-90    A    +    -     +    nC.sub.5 H.sub.11             2Cl          4Cl       oil, base                                             A    +    -     +    nC.sub.5 H.sub.11             3Cl          4Cl       82-86    A    -    -     +    nC.sub.5 H.sub.11             2F                     oil, base                                             B               +    nC.sub.5 H.sub.11             4F                     71-73    A    -    -     +    nC.sub.5 H.sub.11             4Br                    96-99    A    -    -     +    nC.sub.5 H.sub.11             2CH.sub.3    4Cl       75-76,5  B    -    -     +    nC.sub.5 H.sub.11             3Cl          4OCH.sub.3                                    106-108,5                                             B               +    nC.sub.5 H.sub.11             3NO.sub.2              oil, base                                             A    -    +     +    nC.sub.5 H.sub.11             3,4-benzo              80-81    B               +    nC.sub.5 H.sub.11             2,3-benzo              oil, base                                             A    +    -     +    3-methyl                        127-128,5                                             A    -    -     +    butyl                           maleaat    nC.sub.6 H.sub.13               115-116  A    -    +     +                                    maleaat    cyclo                           139,5-142                                             B               +    hexyl                                                    +    nC.sub.7 H.sub.15               112,5-114                                             A    +    +     +                                    maleaat    CH.sub.2 OC.sub.3 H.sub.7       90-91    A    -          +                                    maleaat    __________________________________________________________________________     If nothing is stated in the columns R.sub.3, R.sub.4, R.sub.5, R.sub.6,     the substituent in question is a hydrogen atom.     + active     - not active or substantially not active.

TABLET

50 mgms O-(2-amino-ethyl)4'-methoxy-1'-butyronaphthone oxim HCl

335 mgms lactose

60 mgms of potatoe starch

25 mgms talcum

5 mgms magnesium stearate

5 mgms gelatin

SUPPOSITORY

50 mgms O-(2-amino-ethyl)-3'-chloro-4'-hydroxyhexanophenone oxim HCl

1500 mgms of suppository mass

Injection Liquid

25 gms O-(2-amino-ethyl)4'-methylacetophenone oxim HCl

1.80 gms methyl-p.hydroxybenzoate

0.20 gms propyl-p.hydroxybenzoate

9.0 gms of sodium chloride

4.0 gms polysorbate 80 U.S.P.

water to 1000 mls.

What is claimed is:
 1. A compound of the formula: ##STR12## or saltsthereof with pharmaceutically acceptable acids wherein R₃ is selectedfrom the group consisting of alkoxy alkyl and alkylthio alkyl eachhaving up to eight carbon atoms, and R₆ is a hydrogen atom or a halogenatom, wherein when R₆ is a chlorine atom, R₃ cannot be ethoxybutyl,methoxypentyl, or ethoxypentyl, and when R₆ is a bromine atom, R₃ cannotbe methoxybutyl.
 2. As a compound of claim 1O-(2-amino-ethyl)-2-n.propyloxyacetophenone oxim and salts thereof withpharmaceutically acceptable acids.
 3. As a compound of claim 1O-(2-amino-ethyl)-2-n.propylthioacetophenone oxim and salts thereof withpharmaceutically acceptable acids.
 4. The compound of claim 1 wherein R₃is alkoxyalkyl.
 5. The compound of claim 1 wherein R₆ is a halogen atom.6. The compound of claim 4 wherein R₆ is a halogen atom.